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Deletion of Pdcd5 in mice led to the deficiency of placenta development and embryonic lethality
Ge Li1,2,3,4, Chentong Xu1,2,4, Xin Lin1,2,4
1Department of Immunology, Peking University School of Basic Medical Science, No. 38 Xueyuan Road, Beijing 100191, China.
Abstract:
Programmed cell death 5 (PDCD5) is an apoptosis promoter molecule that displays multiple biological activities. However, the function of PDCD5 in vivo has not yet been investigated. Here, we generated a Pdcd5 knockout mouse model to study the physiological role of PDCD5 in vivo. Knockout of the Pdcd5 gene resulted in embryonic lethality at mid-gestation. Histopathological analysis revealed dysplasia in both the LZs and JZs in Pdcd5-/- placentas with defects in spongiotrophoblasts and trophoblast giant cells. Furthermore, Pdcd5-/- embryos had impaired transplacental passage capacity. We also found that Pdcd5-/- embryos exhibited cardiac abnormalities and defective liver development. The growth defect is linked to impaired placental development and may be caused by insufficient oxygen and nutrient transfer across the placenta. These findings were verified in vitro in Pdcd5 knockout mouse embryonic fibroblasts, which showed increased apoptosis and G0/G1 phase cell cycle arrest. Pdcd5 knockout decreased the Vegf and hepatocyte growth factor (Hgf) levels, downregulated the downstream Pik3ca-Akt-Mtor signal pathway and decreased cell survival. Collectively, our studies demonstrated that Pdcd5 knockout in mouse embryos results in placental defects and embryonic lethality.
Insights
Programmed cell death 5 (PDCD5) knockout causes embryonic lethality in mice due to severe placental defects. This essential gene is vital for placental development, embryonic growth, and survival.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- Programmed cell death 5 (PDCD5) is known to promote apoptosis and possess diverse biological activities.
- The in vivo physiological functions of PDCD5 have remained largely uninvestigated.
Purpose of the Study:
- To elucidate the physiological role of PDCD5 in vivo by generating and analyzing a Pdcd5 knockout mouse model.
Main Methods:
- Generation of a Pdcd5 knockout mouse model.
- Histopathological analysis of placentas and embryos.
- In vitro studies using Pdcd5 knockout mouse embryonic fibroblasts.
Main Results:
- Pdcd5 knockout led to embryonic lethality at mid-gestation.
- Placentas exhibited dysplasia in the labyrinth zone (LZ) and junctional zone (JZ), with defects in spongiotrophoblasts and trophoblast giant cells.
- Pdcd5 knockout embryos showed impaired transplacental nutrient/oxygen transfer, cardiac abnormalities, and defective liver development.
- In vitro, Pdcd5 knockout fibroblasts displayed increased apoptosis and G0/G1 cell cycle arrest, with decreased VEGF, HGF, and impaired PI3K/Akt/mTOR signaling.
Conclusions:
- PDCD5 is crucial for proper placental development and embryonic survival.
- Defects in placental function, including nutrient and oxygen transfer, underlie the observed embryonic lethality and developmental abnormalities.
- PDCD5 plays a critical role in cell survival pathways, including VEGF, HGF, and PI3K/Akt/mTOR signaling.
